Abnormal Expression of Glutamate Transporter and Transporter Interacting Molecules in Prefrontal Cortex in Elderly Patients with Schizophrenia

Overview

Journal Schizophr Res

Specialty Psychiatry

Date 2008 Aug 6

PMID 18678470

Citations 61

Authors

Deborah Bauer

Daya Gupta

Vahram Harotunian

James H Meador-Woodruff

Robert E McCullumsmith

Affiliations

Soon will be listed here.

Abstract

Glutamate cycling is critically important for neurotransmission, and may be altered in schizophrenia. The excitatory amino acid transporters (EAATs) facilitate the reuptake of glutamate from the synaptic cleft and have a key role in glutamate cycling. We hypothesized that expression of the EAATs and the EAAT regulating proteins ARHGEF11, JWA, G-protein suppressor pathway 1 (GPS1), and KIAA0302 are altered in the brain in schizophrenia. To test this, we measured expression of EAAT1, EAAT2, EAAT3, and EAAT interacting proteins in postmortem tissue from the dorsolateral prefrontal and anterior cingulate cortex of patients with schizophrenia and a comparison group using in situ hybridization and Western blot analysis. We found increased EAAT1 transcripts and decreased protein expression, increased EAAT3 transcripts and protein, and elevated protein expression of both GPS1 and KIAA0302 protein. We did not find any changes in expression of EAAT2. These data indicate that proteins involved in glutamate reuptake and cycling are altered in the cortex in schizophrenia, and may provide potential targets for future treatment strategies.

Citing Articles

EAAT2 Activation Regulates Glutamate Excitotoxicity and Reduces Impulsivity in a Rodent Model of Parkinson's Disease.

Das S, McCloskey K, Nepal B, Kortagere S Mol Neurobiol. 2024; .

PMID: 39630405 DOI: 10.1007/s12035-024-04644-0.

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury.

Colon-Mercado J, Torrado-Tapias A, Salgado I, Santiago J, Rivera S, Bracho-Rincon D Neural Regen Res. 2024; 20(11):3317-3329.

PMID: 39314150 PMC: 11881711. DOI: 10.4103/NRR.NRR-D-24-00035.

Neurodevelopmental trajectories, polygenic risk, and lipometabolism in vulnerability and resilience to schizophrenia.

Duan J, Gong X, Womer F, Sun K, Tang L, Liu J BMC Psychiatry. 2023; 23(1):153.

PMID: 36894907 PMC: 9999573. DOI: 10.1186/s12888-023-04597-z.

Gene Expression and Epigenetic Regulation in the Prefrontal Cortex of Schizophrenia.

Bilecki W, Mackowiak M Genes (Basel). 2023; 14(2).

PMID: 36833173 PMC: 9957055. DOI: 10.3390/genes14020243.

Astrocyte regulation of synaptic signaling in psychiatric disorders.

Kruyer A, Kalivas P, Scofield M Neuropsychopharmacology. 2022; 48(1):21-36.

PMID: 35577914 PMC: 9700696. DOI: 10.1038/s41386-022-01338-w.

References

Choe B, Kim K, Suh T, Lee C, Paik I, BAHK Y . 1H magnetic resonance spectroscopy characterization of neuronal dysfunction in drug-naive, chronic schizophrenia. Acad Radiol. 1994; 1(3):211-6. DOI: 10.1016/s1076-6332(05)80716-0. View

McCullumsmith R, Meador-Woodruff J . Striatal excitatory amino acid transporter transcript expression in schizophrenia, bipolar disorder, and major depressive disorder. Neuropsychopharmacology. 2002; 26(3):368-75. DOI: 10.1016/S0893-133X(01)00370-0. View

Meador-Woodruff J, Davis K, Haroutunian V . Abnormal kainate receptor expression in prefrontal cortex in schizophrenia. Neuropsychopharmacology. 2001; 24(5):545-52. DOI: 10.1016/S0893-133X(00)00189-5. View

Danbolt N . Glutamate uptake. Prog Neurobiol. 2001; 65(1):1-105. DOI: 10.1016/s0301-0082(00)00067-8. View

Quintana J, Wong T, Ortiz-Portillo E, Marder S, Mazziotta J . Anterior cingulate dysfunction during choice anticipation in schizophrenia. Psychiatry Res. 2004; 132(2):117-30. DOI: 10.1016/j.pscychresns.2004.06.005. View

Melone M, Vitellaro-Zuccarello L, Vallejo-Illarramendi A, Matute C, Cozzi A, Pellegrini-Giampietro D . The expression of glutamate transporter GLT-1 in the rat cerebral cortex is down-regulated by the antipsychotic drug clozapine. Mol Psychiatry. 2001; 6(4):380-6. DOI: 10.1038/sj.mp.4000880. View

Perry T . Normal cerebrospinal fluid and brain glutamate levels in schizophrenia do not support the hypothesis of glutamatergic neuronal dysfunction. Neurosci Lett. 1982; 28(1):81-5. DOI: 10.1016/0304-3940(82)90212-9. View

Gattaz W, Gasser T, Beckmann H . Multidimensional analysis of the concentrations of 17 substances in the CSF of schizophrenics and controls. Biol Psychiatry. 1985; 20(4):360-6. DOI: 10.1016/0006-3223(85)90038-1. View

ITIL T, Keskiner A, Kiremitci N, Holden J . Effect of phencyclidine in chronic schizophrenics. Can Psychiatr Assoc J. 1967; 12(2):209-12. DOI: 10.1177/070674376701200217. View

10.

Lauriat T, Dracheva S, Chin B, Schmeidler J, McInnes L, Haroutunian V . Quantitative analysis of glutamate transporter mRNA expression in prefrontal and primary visual cortex in normal and schizophrenic brain. Neuroscience. 2005; 137(3):843-51. DOI: 10.1016/j.neuroscience.2005.10.003. View

11.

Arriza J, Eliasof S, Kavanaugh M, Amara S . Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc Natl Acad Sci U S A. 1997; 94(8):4155-60. PMC: 20584. DOI: 10.1073/pnas.94.8.4155. View

12.

Smith R, Haroutunian V, Davis K, Meador-Woodruff J . Vesicular glutamate transporter transcript expression in the thalamus in schizophrenia. Neuroreport. 2001; 12(13):2885-7. DOI: 10.1097/00001756-200109170-00026. View

13.

Rothstein J, Pardo C, Bristol L, Jin L, Kuncl R, Kanai Y . Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron. 1996; 16(3):675-86. DOI: 10.1016/s0896-6273(00)80086-0. View

14.

Huerta I, McCullumsmith R, Haroutunian V, Gimenez-Amaya J, Meador-Woodruff J . Expression of excitatory amino acid transporter interacting protein transcripts in the thalamus in schizophrenia. Synapse. 2006; 59(7):394-402. DOI: 10.1002/syn.20250. View

15.

Korpi E, Kaufmann C, Marnela K, Weinberger D . Cerebrospinal fluid amino acid concentrations in chronic schizophrenia. Psychiatry Res. 1987; 20(4):337-45. DOI: 10.1016/0165-1781(87)90095-3. View

16.

Aanonsen L, Wilcox G . Phencyclidine selectively blocks a spinal action of N-methyl-D-aspartate in mice. Neurosci Lett. 1986; 67(2):191-7. DOI: 10.1016/0304-3940(86)90396-4. View

17.

Coyle J . The glutamatergic dysfunction hypothesis for schizophrenia. Harv Rev Psychiatry. 1996; 3(5):241-53. DOI: 10.3109/10673229609017192. View

18.

Stan A, Ghose S, Gao X, Roberts R, Lewis-Amezcua K, Hatanpaa K . Human postmortem tissue: what quality markers matter?. Brain Res. 2006; 1123(1):1-11. PMC: 1995236. DOI: 10.1016/j.brainres.2006.09.025. View

19.

Deutsch S, Mastropaolo J, Schwartz B, Rosse R, Morihisa J . A "glutamatergic hypothesis" of schizophrenia. Rationale for pharmacotherapy with glycine. Clin Neuropharmacol. 1989; 12(1):1-13. View

20.

Deicken R, Zhou L, Schuff N, Weiner M . Proton magnetic resonance spectroscopy of the anterior cingulate region in schizophrenia. Schizophr Res. 1997; 27(1):65-71. DOI: 10.1016/S0920-9964(97)00082-0. View